{"title":"人类 GDAP1 基因的表观遗传调控","authors":"","doi":"10.1016/j.bbrep.2024.101827","DOIUrl":null,"url":null,"abstract":"<div><p>Mutations in the ganglioside-induced differentiation-associated protein 1 (<em>GDAP1</em>) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating <em>GDAP1</em> expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the <em>GDAP1</em> gene inhibits its activity. Treating cells with low <em>GDAP1</em> expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the <em>GDAP1</em> promoter. Thus, we identified a mechanism that could be used to manipulate <em>GDAP1</em> expression.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001912/pdfft?md5=f9fd08807cb4fb17253e8d0588917795&pid=1-s2.0-S2405580824001912-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Epigenetic regulation of the human GDAP1 gene\",\"authors\":\"\",\"doi\":\"10.1016/j.bbrep.2024.101827\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Mutations in the ganglioside-induced differentiation-associated protein 1 (<em>GDAP1</em>) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating <em>GDAP1</em> expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the <em>GDAP1</em> gene inhibits its activity. Treating cells with low <em>GDAP1</em> expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the <em>GDAP1</em> promoter. Thus, we identified a mechanism that could be used to manipulate <em>GDAP1</em> expression.</p></div>\",\"PeriodicalId\":8771,\"journal\":{\"name\":\"Biochemistry and Biophysics Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2405580824001912/pdfft?md5=f9fd08807cb4fb17253e8d0588917795&pid=1-s2.0-S2405580824001912-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry and Biophysics Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2405580824001912\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry and Biophysics Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405580824001912","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating GDAP1 expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the GDAP1 gene inhibits its activity. Treating cells with low GDAP1 expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the GDAP1 promoter. Thus, we identified a mechanism that could be used to manipulate GDAP1 expression.
期刊介绍:
Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.